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Cerebral Cortex (New York, N.Y. : 1991) Jul 2022Striatal loci are connected to both the ipsilateral and contralateral frontal cortex. Normative quantitation of the dissimilarity between striatal loci's hemispheric...
Striatal loci are connected to both the ipsilateral and contralateral frontal cortex. Normative quantitation of the dissimilarity between striatal loci's hemispheric connection profiles and its spatial variance across the striatum, and assessment of how interindividual differences relate to function, stands to further the understanding of the role of corticostriatal circuits in lateralized functions and the role of abnormal corticostriatal laterality in neurodevelopmental and other neuropsychiatric disorders. A resting-state functional connectivity fingerprinting approach (n = 261) identified "laterality hotspots"-loci whose profiles of connectivity with ipsilateral and contralateral frontal cortex were disproportionately dissimilar-in the right rostral ventral putamen, left rostral central caudate, and bilateral caudal ventral caudate. Findings were replicated in an independent sample and were robust to both preprocessing choices and the choice of cortical atlas used for parcellation definitions. Across subjects, greater rightward connectional laterality at the right ventral putamen hotspot and greater leftward connectional laterality at the left rostral caudate hotspot were associated with higher performance on tasks engaging lateralized functions (i.e., response inhibition and language, respectively). In sum, we find robust and reproducible evidence for striatal loci with disproportionately lateralized connectivity profiles where interindividual differences in laterality magnitude are associated with behavioral capacities on lateralized functions.
Topics: Brain Mapping; Corpus Striatum; Functional Laterality; Humans; Magnetic Resonance Imaging; Neural Pathways; Putamen
PubMed: 34727171
DOI: 10.1093/cercor/bhab392 -
Journal of Psychopharmacology (Oxford,... Dec 2022Previous magnetic resonance imaging studies in regular cannabis users report altered grey matter volume (GMV) in brain regions, including the prefrontal cortex (PFC),...
BACKGROUND
Previous magnetic resonance imaging studies in regular cannabis users report altered grey matter volume (GMV) in brain regions, including the prefrontal cortex (PFC), putamen and hippocampus. However, most studies have tended to recruit recreational users with high levels of cannabis use, and have not controlled for the possible confounding effects of tobacco use. We attempt to address these limitations in the present study.
METHODS
We acquired volumetric images in sex, age and IQ-matched groups of (1) regular Cannabis users who also smoke Tobacco cigarettes ('CT'; = 33), (2) non-cannabis-using Tobacco cigarette smokers ('T'; = 19) and (3) non-cannabis/tobacco-using Controls ('C'; = 35). GMV in bilateral PFC, putamen and hippocampal regions was compared across groups. We also examined the associations between GMV differences and levels of cannabis and tobacco use, measures of intellectual function, and of depression, anxiety and stress.
RESULTS
Relative to controls, both CT and T groups showed lower GMV in the left inferior frontal gyrus, and greater GMV in the putamen. In addition, lower GMV in the right frontal pole in the CT group (but not the T group) was associated with lifetime cannabis use, but not with cigarette use.
CONCLUSIONS
Regular cannabis users who also smoked tobacco cigarettes showed altered GMV patterns relative to controls. However, a similar pattern of GMV differences was also seen between regular tobacco users that did not use cannabis. Further research is needed to disentangle the effects of cannabis and tobacco use on brain structure.
Topics: Gray Matter; Nicotiana; Cannabis; Putamen; Prefrontal Cortex; Magnetic Resonance Imaging
PubMed: 36112825
DOI: 10.1177/02698811221117523 -
Journal of Neurochemistry Mar 2020The dorsal striatum coordinates input-output processing of numerous functions including those related to motor activity, motivation, and learning. Considerable...
Old neurochemical markers, new functional directions?: An Editorial for 'Distinct gradients of various neurotransmitter markers in caudate nucleus and putamen of the human brain' on page 650.
The dorsal striatum coordinates input-output processing of numerous functions including those related to motor activity, motivation, and learning. Considerable anatomical and biochemical heterogeneity across striatal subregions has long been known to result in distinct functional outcomes, and for imbalances in these pathways to contribute to many complex disorders. Here we highlight the study of Hörtnagl et al. (2019) who utilize precision dissection of human caudate nucleus and putamen for detailed measurement of major neurochemical markers to address the question of anatomical heterogeneity of neurotransmitter distribution and turnover in these regions. The findings identify gradients of neurotransmitter markers in rostro-caudal, dorso-lateral, and anterior-posterior directions with a precision that has not been previously determined in humans. Correlative analyses of the results also suggest tentative links between content of various neurotransmitters in specific subregions, raising the intriguing possibility that neurotransmitter quantity in one territory may correlate with the quantity of the same or different transmitter from another territory. This suggests the presence of a functional anatomy over extensive brain regions and networks that can be studied through multiple correlative analyses, and identify a possible basis for a new approach for postmortem analysis of neurotransmitter distribution and function.
Topics: Aged; Biomarkers; Caudate Nucleus; Female; Humans; Male; Neurotransmitter Agents; Postmortem Changes; Putamen
PubMed: 31917872
DOI: 10.1111/jnc.14929 -
Nature Communications Jul 2023The ability to use blood to predict the outcomes of Parkinson's disease, including disease progression and cognitive and motor complications, would be of significant...
The ability to use blood to predict the outcomes of Parkinson's disease, including disease progression and cognitive and motor complications, would be of significant clinical value. We undertook bulk RNA sequencing from the caudate and putamen of postmortem Parkinson's disease (n = 35) and control (n = 40) striatum, and compared molecular profiles with clinical features and bulk RNA sequencing data obtained from antemortem peripheral blood. Cognitive and motor complications of Parkinson's disease were associated with molecular changes in the caudate (stress response) and putamen (endothelial pathways) respectively. Later and earlier-onset Parkinson's disease were molecularly distinct, and disease duration was associated with changes in caudate (oligodendrocyte development) and putamen (cellular senescence), respectively. Transcriptome patterns in the postmortem Parkinson's disease brain were also evident in antemortem peripheral blood, and correlated with clinical features of the disease. Together, these findings identify molecular signatures in Parkinson's disease patients' brain and blood of potential pathophysiologic and prognostic importance.
Topics: Humans; Parkinson Disease; Transcriptome; Brain; Corpus Striatum; Putamen
PubMed: 37407548
DOI: 10.1038/s41467-023-39652-6 -
The Journal of Neuroscience : the... Sep 2022In nonhuman primates, major input to the striatum originates from ipsilateral cortex and thalamus. The striatum is a target also of crossed corticostriatal (CSt)...
In nonhuman primates, major input to the striatum originates from ipsilateral cortex and thalamus. The striatum is a target also of crossed corticostriatal (CSt) projections from the contralateral hemisphere, which have been so far somewhat neglected. In the present study, based on neural tracer injections in different parts of the striatum in macaques of either sex, we analyzed and compared qualitatively and quantitatively the distribution of labeled CSt cells in the two hemispheres. The results showed that crossed CSt projections to the caudate and the putamen can be relatively robust (up to 30% of total labeled cells). The origin of the direct and the crossed CSt projections was not symmetrical as the crossed ones originated almost exclusively from motor, prefrontal, and cingulate areas and not from parietal and temporal areas. Furthermore, there were several cases in which the contribution of contralateral areas tended to equal that of the ipsilateral ones. The present study is the first detailed description of this anatomic pathway of the macaque brain and provides the substrate for bilateral distribution of motor, motivational, and cognitive signals for reinforcement learning and selection of actions or action sequences, and for learning compensatory motor strategies after cortical stroke. In nonhuman primates the striatum is a target of projections originating from the contralateral hemisphere (crossed CSt projections), which have been so far poorly investigated. The present study analyzed qualitatively and quantitatively in the macaque brain the origin of the crossed CSt projections compared with those originating from the ipsilateral hemisphere. The results showed that crossed CSt projections originate mostly from frontal and rostral cingulate areas and in some cases their contribution tended to equal that from ipsilateral areas. These projections could provide the substrate for bilateral distribution of motor, motivational, and cognitive signals for reinforcement learning and action selection, and for learning compensatory motor strategies after cortical stroke.
Topics: Animals; Brain Mapping; Corpus Striatum; Macaca; Neural Pathways; Putamen; Stroke
PubMed: 35953294
DOI: 10.1523/JNEUROSCI.0071-22.2022 -
Biological Psychiatry Jan 2023Psychosis is a defining feature of schizophrenia and highly prevalent in bipolar disorder. Notably, individuals with these illnesses also have major disruptions in sleep...
BACKGROUND
Psychosis is a defining feature of schizophrenia and highly prevalent in bipolar disorder. Notably, individuals with these illnesses also have major disruptions in sleep and circadian rhythms, and disturbances of sleep and circadian rhythms can precipitate or exacerbate psychotic symptoms. Psychosis is associated with the striatum, though to our knowledge, no study to date has directly measured molecular rhythms and determined how they are altered in the striatum of subjects with psychosis.
METHODS
We performed RNA sequencing and both differential expression and rhythmicity analyses to investigate diurnal alterations in gene expression in human postmortem striatal subregions (nucleus accumbens, caudate, and putamen) in subjects with psychosis (n = 36) relative to unaffected comparison subjects (n = 36).
RESULTS
Across regions, we found differential expression of immune-related transcripts and a substantial loss of rhythmicity in core circadian clock genes in subjects with psychosis. In the nucleus accumbens, mitochondrial-related transcripts had decreased expression in subjects with psychosis, but only in those who died at night. Additionally, we found a loss of rhythmicity in small nucleolar RNAs and a gain of rhythmicity in glutamatergic signaling in the nucleus accumbens of subjects with psychosis. Between-region comparisons indicated that rhythmicity in the caudate and putamen was far more similar in subjects with psychosis than in matched comparison subjects.
CONCLUSIONS
Together, these findings reveal differential and rhythmic gene expression differences across the striatum that may contribute to striatal dysfunction and psychosis in psychotic disorders.
Topics: Humans; Psychotic Disorders; Circadian Rhythm; Corpus Striatum; Putamen; Gene Expression
PubMed: 36302706
DOI: 10.1016/j.biopsych.2022.08.013 -
Brain : a Journal of Neurology Apr 2022The striatal dopaminergic deficit in Parkinson's disease exhibits a typical pattern, extending from the caudal and dorsal putamen at onset to its more rostral region as...
The striatal dopaminergic deficit in Parkinson's disease exhibits a typical pattern, extending from the caudal and dorsal putamen at onset to its more rostral region as the disease progresses. Clinically, upper-limb onset of cardinal motor features is the rule. Thus, according to current understanding of striatal somatotopy (i.e. the lower limb is dorsal to the upper limb) the assumed pattern of early dorsal striatal dopaminergic denervation in Parkinson's disease does not fit with an upper-limb onset. We have examined the topography of putaminal denervation in a cohort of 23 recently diagnosed de novo Parkinson's disease patients and 19 age-/gender-matched healthy subjects assessed clinically and by 18F-DOPA PET; 15 patients were re-assessed after 2 years. There was a net upper-limb predominance of motor features at onset. Caudal denervation of the putamen was confirmed in both the more- and less-affected hemispheres and corresponding hemibodies. Spatial covariance analysis of the most affected hemisphere revealed a pattern of 18F-DOPA uptake rate deficit that suggested focal dopamine loss starting in the posterolateral and intermediate putamen. Functional MRI group-activation maps during a self-paced motor task were used to represent the somatotopy of the putamen and were then used to characterize the decline in 18F-DOPA uptake rate in the upper- and lower-limb territories. This showed a predominant decrement in both hemispheres, which correlated significantly with severity of bradykinesia. A more detailed spatial analysis revealed a dorsoventral linear gradient of 18F-DOPA uptake rate in Parkinson's disease patients, with the highest putamen denervation in the caudal intermediate subregion (dorsoventral plane) compared to healthy subjects. The latter area coincides with the functional representation of the upper limb. Clinical motor assessment at 2-year follow-up showed modest worsening of parkinsonism in the primarily affected side and more noticeable increases in the upper limb in the less-affected side. Concomitantly, 18F-DOPA uptake rate in the less-affected putamen mimicked that recognized on the most-affected side. Our findings suggest that early dopaminergic denervation in Parkinson's disease follows a somatotopically related pattern, starting with the upper-limb representation in the putamen and progressing over a 2-year period in the less-affected hemisphere. These changes correlate well with the clinical presentation and evolution of motor features. Recognition of a precise somatotopic onset of nigrostriatal denervation may help to better understand the onset and progression of dopaminergic neurodegeneration in Parkinson's disease and eventually monitor the impact of putative therapies.
Topics: Child, Preschool; Corpus Striatum; Denervation; Dihydroxyphenylalanine; Dopamine; Humans; Parkinson Disease; Putamen
PubMed: 35349639
DOI: 10.1093/brain/awab378 -
BioRxiv : the Preprint Server For... Aug 2023Age is a major common risk factor underlying neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Previous...
Age is a major common risk factor underlying neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Previous studies reported that chronological age correlates with differential gene expression across different brain regions. However, prior datasets have not disambiguated whether expression associations with age are due to changes in cell numbers and/or gene expression per cell. In this study, we leveraged single nucleus RNA-sequencing (snRNAseq) to examine changes in cell proportions and transcriptomes in four different brain regions, each from 12 donors aged 20-30 years (young) or 60-85 years (old). We sampled 155,192 nuclei from two cortical regions (entorhinal cortex and middle temporal gyrus) and two subcortical regions (putamen and subventricular zone) relevant to neurodegenerative diseases or the proliferative niche. We found no changes in cellular composition of different brain regions with healthy aging. Surprisingly, we did find that each brain region has a distinct aging signature, with only minor overlap in differentially associated genes across regions. Moreover, each cell type shows distinct age-associated expression changes, including loss of protein synthesis genes in cortical inhibitory neurons, axonogenesis genes in excitatory neurons and oligodendrocyte precursor cells, enhanced gliosis markers in astrocytes and disease-associated markers in microglia, and genes critical for neuron-glia communication. Importantly, we find cell type-specific enrichments of age associations with genes nominated by Alzheimer's disease and Parkinson's disease genome-wide association studies (GWAS), such as apolipoprotein E (), and leucine-rich repeat kinase 2 () in microglia that are independent of overall expression levels across cell types. We present this data as a new resource which highlights, first, region- and cell type-specific transcriptomic changes in healthy aging that may contribute to selective vulnerability and, second, provide context for testing GWAS-nominated disease risk genes in relevant subtypes and developing more targeted therapeutic strategies. The data is readily accessible without requirement for extensive computational support in a public website, https://brainexp-hykyffa56a-uc.a.run.app/.
PubMed: 37577533
DOI: 10.1101/2023.07.31.551097 -
NeuroImage. Clinical 2022Patients with Parkinson disease (PD) may show impairments in the social perception. Whether these deficits have been consistently reported, it remains to be clarified... (Meta-Analysis)
Meta-Analysis Review
Patients with Parkinson disease (PD) may show impairments in the social perception. Whether these deficits have been consistently reported, it remains to be clarified which brain alterations subtend them. To this aim, we conducted a neuroimaging meta-analysis to compare the brain activity during social perception in patients with PD versus healthy controls. Our results show that PD patients exhibit a significantly decreased response in the basal ganglia (putamen and pallidum) and a trend toward decreased activity in the mirror system, particularly in the left parietal cortex (inferior parietal lobule and intraparietal sulcus). This reduced activation may be tied to a disruption of cognitive resonance mechanisms and may thus constitute the basis of impaired others' representations underlying action and emotion perception. We also found increased activation in the posterior cerebellum in PD, although only in a within-group analysis and not in comparison with healthy controls. This cerebellar activation may reflect compensatory mechanisms, an aspect that deserves further investigation. We discuss the clinical implications of our findings for the development of novel social skill training programs for PD patients.
Topics: Emotions; Humans; Magnetic Resonance Imaging; Neuroimaging; Parkinson Disease; Perception
PubMed: 35569229
DOI: 10.1016/j.nicl.2022.103031 -
Addiction Biology Mar 2021The gray matter volume (GMV) of the putamen has been reported to be regulated by kinectin 1 gene (KTN1). As a hub of the dopaminergic circuit, the putamen is widely...
The gray matter volume (GMV) of the putamen has been reported to be regulated by kinectin 1 gene (KTN1). As a hub of the dopaminergic circuit, the putamen is widely implicated in the etiological processes of substance use disorders (SUD). Here, we aimed to identify robust and reliable associations between KTN1 SNPs and SUD across multiple samples. We examined the associations between SUD and KTN1 SNPs in four independent population-based or family-based samples (n = 10,209). The potential regulatory effects of the risk alleles on the putamen GMVs, the effects of alcohol, nicotine, marijuana and cocaine on KTN1 mRNA expression, and the relationship between KTN1 mRNA expression and SUD were explored. We found that a total of 23 SNPs were associated with SUD across at least two independent samples (1.4 × 10 ≤ p ≤ 0.049), including one SNP (rs12895072) across three samples (8.8 × 10 ≤ p ≤ 0.049). Four other SNPs were significantly or suggestively associated with SUD only in European-Australians (4.8 × 10 ≤ p ≤ 0.058). All of the SUD-risk alleles of these 27 SNPs increased (β > 0) the putamen GMVs and represented major alleles (f > 0.5) in Europeans. Twenty-two SNPs were potentially biologically functional. Alcohol, nicotine and cocaine significantly affected the KTN1 mRNA expression, and the KTN1 mRNA was differentially expressed between nicotine or cocaine dependent and control subjects. We concluded that there was a replicable and robust relationship among the KTN1 variants, KTN1 mRNA expression, putamen GMVs, molecular effects of substances, and SUD, suggesting that some risk KTN1 alleles might increase kinectin 1 expression in the putamen, altering putamen structures and functions, and leading to SUD.
Topics: Alcoholism; Alleles; Australia; Comorbidity; Female; Genetic Predisposition to Disease; Gray Matter; Humans; Male; Marijuana Abuse; Membrane Proteins; Polymorphism, Single Nucleotide; Putamen; RNA, Messenger; Substance-Related Disorders; Tobacco Use Disorder; White People
PubMed: 32115811
DOI: 10.1111/adb.12888